Massive efforts by the pharmaceutical industry to develop anticancer drugs via high throughput screening of large chemical libraries and structure based designs for targeted tumor therapy have so far yielded poor returns. The majority of anticancer drugs presently used in clinical practice are based on natural product chemistry. Thus the search for improved cancer therapeutics from natural resources with novel mechanisms of drug action has gained renewed relevance. A drug screening program of small molecules from marine environments has lead to the discovery of a family of secondary metabolites from cyanobacterium. These pluripotent lipopeptides exhibit nanomolar potencies against tumor cells.
An extract from a Lyngbya majusculal Schizothrix sp. mixed assemblage of marine cyanobacteria led to the discovery of somocystinamide A, an extraordinary disulfide dimer of mixed polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS), or “PKS/NRPS,” biosynthetic origin. See, e.g., Nogle, et al. (2002) Org. Lett., 4(7):1095-1098. Somocystinamide A was shown to exhibit significant cytotoxicity against mouse neuro-2a neuroblastoma cells (with an IC50=1.4 μg/mL); see e.g., Nogle (id).
Vascular Endothelial Growth Factor (VEGF) is a selective angiogenic growth factor that can stimulate endothelial cell mitogenesis. Human tumor biopsies exhibit enhanced expression of VEGF mRNAs by malignant cells and VEGF receptor mRNAs in adjacent endothelial cells.